Grubisa Ivana, Otasevic Petar, Vucinic Nada, Milicic Biljana, Jozic Tanja, Krstic Slobodan, Milasin Jelena
Department of Human Genetics and Prenatal Diagnostics, Zvezdara, University Medical Center, University of Belgrade, Belgrade, Serbia.
Dedinje Cardiovascular Institute Belgrade, Serbia.
Genet Mol Biol. 2018 Jan-Mar;41(1):35-40. doi: 10.1590/1678-4685-GMB-2017-0034.
Oxidative stress (OS) plays an important role in atherogenesis and since glutathione S-transferases (GSTs) provide protection against OS, we have tested the hypothesis that deletion polymorphisms in two GSTs (GSTM1 and GSTT1) may affect the risk of developing atherosclerosis. A total of 382 individuals (200 patients with atherosclerosis and 182 healthy controls) were included in this association study. Genomic DNA was isolated from peripheral blood cells or from buccal epithelial cells and genotyping was performed using multiplex-PCR or real-time PCR methods. GSTM1 null genotype was significantly more frequent in atherosclerotic patients than in controls (52.0% vs 34.1%) and individuals with the GSTM1 null genotype had an approximately 2-fold increase in atherosclerosis risk (OR: 2.1, 95%CI=1.39-3.17, P=0.0004). GSTT1 null genotype alone did not show a statistically significant effect on atherosclerosis risk modulation, but the association approached significance (OR: 1.57, 95%CI=0.94-2.64, P=0.08). The combined analysis showed that the presence of both genes had a protective effect against atherosclerosis (OR=0.55, 95%CI=0.37-0.83, P=0.005) while double null genotypes led to a robust atherosclerosis risk increase (OR: 8.14, 95%CI= 2.41-27.51, P < 0.0001). This study demonstrated that the GSTM1 null and combined GSTM1/GSTT1 null genotypes are susceptibility factors for development of atherosclerosis in a Serbian population.
氧化应激（OS）在动脉粥样硬化的发生发展中起重要作用，由于谷胱甘肽S-转移酶（GSTs）可提供针对OS的保护作用，我们检验了以下假设：两种GSTs（GSTM1和GSTT1）的缺失多态性可能会影响动脉粥样硬化的发病风险。本关联研究共纳入了382名个体（200例动脉粥样硬化患者和182名健康对照）。从外周血细胞或颊黏膜上皮细胞中提取基因组DNA，并使用多重PCR或实时PCR方法进行基因分型。GSTM1缺失基因型在动脉粥样硬化患者中的出现频率显著高于对照组（52.0%对34.1%），且具有GSTM1缺失基因型的个体患动脉粥样硬化的风险增加了约2倍（比值比：2.1，95%置信区间=1.39 - 3.17，P = 0.0004）。单独的GSTT1缺失基因型对动脉粥样硬化风险调节未显示出统计学上的显著影响，但该关联接近显著水平（比值比：1.57，95%置信区间=0.94 - 2.64，P = 0.08）。联合分析表明，两个基因均存在对动脉粥样硬化具有保护作用（比值比=0.55，95%置信区间=0.37 - 0.83，P = 0.005），而双重缺失基因型则导致动脉粥样硬化风险显著增加（比值比：8.14，95%置信区间=2.41 - 27.51，P < 0.0001）。本研究表明，在塞尔维亚人群中，GSTM1缺失基因型以及联合的GSTM1/GSTT1缺失基因型是动脉粥样硬化发生的易感因素。
